TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8393	25402;25403;25404	chr2:178717697;178717696;178717695	chr2:179582424;179582423;179582422
N2AB	8076	24451;24452;24453	chr2:178717697;178717696;178717695	chr2:179582424;179582423;179582422
N2A	7149	21670;21671;21672	chr2:178717697;178717696;178717695	chr2:179582424;179582423;179582422
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-69
• Domain position: 34
• Structural Position: 48
• Q(SASA): 0.1448
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
W/L	None	None	1.0	D	0.806	0.721	0.944499737478	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	1.01626E-03	None	0	0	None	0	0	0	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
W/A	0.9934	likely_pathogenic	0.9962	pathogenic	-2.85	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
W/C	0.9958	likely_pathogenic	0.9977	pathogenic	-1.498	Destabilizing	1.0	D	0.805	deleterious	D	0.707708745	None	None	N
W/D	0.9996	likely_pathogenic	0.9997	pathogenic	-3.101	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
W/E	0.9994	likely_pathogenic	0.9996	pathogenic	-2.969	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
W/F	0.6111	likely_pathogenic	0.5997	pathogenic	-1.688	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
W/G	0.98	likely_pathogenic	0.9884	pathogenic	-3.104	Highly Destabilizing	1.0	D	0.806	deleterious	D	0.707506941	None	None	N
W/H	0.9968	likely_pathogenic	0.9979	pathogenic	-2.205	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
W/I	0.9748	likely_pathogenic	0.983	pathogenic	-1.887	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
W/K	0.9997	likely_pathogenic	0.9998	pathogenic	-2.159	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
W/L	0.9394	likely_pathogenic	0.9596	pathogenic	-1.887	Destabilizing	1.0	D	0.806	deleterious	D	0.69148758	None	None	N
W/M	0.9895	likely_pathogenic	0.9933	pathogenic	-1.431	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
W/N	0.9992	likely_pathogenic	0.9996	pathogenic	-2.862	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
W/P	0.9987	likely_pathogenic	0.9991	pathogenic	-2.237	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
W/Q	0.9995	likely_pathogenic	0.9998	pathogenic	-2.659	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
W/R	0.9989	likely_pathogenic	0.9994	pathogenic	-2.021	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.707708745	None	None	N
W/S	0.9912	likely_pathogenic	0.9954	pathogenic	-3.035	Highly Destabilizing	1.0	D	0.867	deleterious	D	0.707708745	None	None	N
W/T	0.9943	likely_pathogenic	0.9967	pathogenic	-2.826	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
W/V	0.9749	likely_pathogenic	0.9838	pathogenic	-2.237	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
W/Y	0.9325	likely_pathogenic	0.9459	pathogenic	-1.491	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.